ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.221G>C (p.Arg74Pro) (rs886039022)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000243062 SCV000319693 uncertain significance Cardiovascular phenotype 2019-10-02 criteria provided, single submitter clinical testing The p.R74P variant (also known as c.221G>C), located in coding exon 5 of the TNNI3 gene, results from a G to C substitution at nucleotide position 221. The arginine at codon 74 is replaced by proline, an amino acid with dissimilar properties. This alteration was reported as homozygous in a male diagnosed with dilated cardiomyopathy (DCM) at age 13 (Boda U et al. J of Genet. 2009;88(3):373-7); however, it has also been observed in a control in another study (Satyanarayana ML et al. Int J Hum Genet. 2013(4);13:177-81). Other variants affecting this codon (p.R74G and p.R74S) have been reported in cardiomyopathy cohorts; however, details were limited (Cecconi M et al. Int. J. Mol. Med., 2016 Oct;38:1111-24; Hayashi T et al. J. Hum. Genet., 2018 Sep;63:989-996). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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